To evaluate the first-in-human safety, tolerability and food effect of ABBV-CLS-7262 in healthy subjects.

ABBV-CLS-7262 is in development as a CNS-penetrant small molecule activator of eIF2B, which is the guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 (eIF2). eIF2 is an important node in the Integrated Stress Response, which is believed to be persistently activated in various neurological diseases, including amyotrophic lateral sclerosis. By activating eIF2B, ABBV-CLS7262 may attenuate the Integrated Stress Response and restore protein translation.

This multi-part Phase 1 study enrolled healthy male and female subjects between 18 and 65 years of age. A total of 125 subjects received ABBV-CLS-7262 and 33 received placebo.

ABBV-CLS-7262 was well-tolerated following oral administration of single and multiple ascending doses for up to 14 days. All adverse events (AEs) were mild to moderate in severity, and no dose-dependent patterns of AEs or laboratory abnormalities were identified. Following administration with a high-fat meal, the safety, tolerability, and pharmacokinetics were similar when compared to the fasting state.

The observed safety, tolerability, and clinical pharmacology profile of ABBV-CLS-7262 support investigation of the product in further studies.